Is STAR p.Ser12Arg (c.36C>A) pathogenic?

STAR p.Ser12Arg (c.36C>A) is classified Uncertain significance in STAR (ClinVar, No assertion criteria, 1 submitter; last evaluated 2025-01-22). AlphaMissense: likely pathogenic (0.8528); Very rare (popmax 6.22e-05%); Associated with congenital lipoid adrenal hyperplasia due to STAR deficency.

What condition is associated with STAR p.Ser12Arg (c.36C>A)?

STAR p.Ser12Arg (c.36C>A) is associated with congenital lipoid adrenal hyperplasia due to STAR deficency (ClinVar).

How common is STAR p.Ser12Arg (c.36C>A) in the general population?

STAR p.Ser12Arg (c.36C>A) is very rare (popmax 6.22e-05%) (gnomAD).

What do computational predictors say about STAR p.Ser12Arg (c.36C>A)?

AlphaMissense predicts likely pathogenic (score 0.8528) — an in-silico prediction, not a clinical call.

STAR p.Ser12Arg

Q: How is Congenital lipoid adrenal hyperplasia due to STAR deficency inherited?

Typically Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

c.36C>A · VCV4062016

Uncertain significance No assertion criteria

Classification

Uncertain significance

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8528 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 6.22e-05%)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

congenital lipoid adrenal hyperplasia due to STAR deficency

Computational evidence

Protein change
AlphaMissense	0.8528	likely pathogenic
REVEL	0.488	indeterminate
SaProt	LLR -6.44	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL is indeterminate.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 5.9	GERP 0.87, phastCons 1
Regional constraint	o/e 0.99	unconstrained · MANE · 6,542 bp · p 0.84 · regional, not allelic
Overall
CADD	23.3	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 6.22e-05%

Overall 6.22e-05% 1/1,607,134 alleles · very rare exomes 1/1,454,880 · genomes 0/152,254 · joint denominator

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: STAR
Protein: p.Ser12Arg
Coding: c.36C>A
MANE Select: NM_000349
Type: single nucleotide variant
Location: chr8:38150783 (GRCh38)
Gene constraint: LOEUF 1.297 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 82.71 · 4 PDB

Full STAR gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

congenital lipoid adrenal hyperplasia due to STAR deficency — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Congenital lipoid adrenal hyperplasia due to STAR deficency (Orphanet):

Inheritance: Autosomal recessive
Onset: Childhood, Infancy, Neonatal

Similar variants

STAR c.178+1G>C Likely pathogenic ★★ same condition
STAR c.306+1G>A Likely pathogenic ★★ same condition
STAR c.307-1G>C Likely pathogenic ★★ same condition
STAR c.465+2T>C Pathogenic/Likely pathogenic ★★ same condition
STAR c.64+1G>A Pathogenic/Likely pathogenic ★★ same condition
STAR c.64+1G>T Pathogenic ★★ same condition
STAR p.Ala218Val Pathogenic ★★ same condition
STAR p.Arg182Cys Pathogenic ★★ same condition

Built on 18 open, versioned datasets — ClinVar, gnomAD, AlphaMissense, REVEL, ClinGen & more — plus Sugi Variant's own cross-source analysis. Source data 2026-01–2026-10, ClinVar 2026-10. Full sources & versions →

Cite Sugi Variant

Gür T. Sugi Variant: A Deterministic Per-Variant Germline Reference from a Knowledge Graph for Humans and AI Agents. 2026. doi:10.5281/zenodo.21509445. This variant: https://sugi.bio/variant/star-p-ser12arg (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown